β-Hairpin-Mediated Formation of Structurally Distinct Multimers of Neurotoxic Prion Peptides

β-Hairpin-Mediated Formation of Structurally Distinct Multimers of Neurotoxic Prion Peptides

Protein misfolding disorders are associated with conformational changes in specific proteins, leading to the formation of potentially neurotoxic amyloid fibrils. During pathogenesis of prion disease, the prion protein misfolds into β-sheet rich, protease-resistant isoforms. A key, hydrophobic domain within the prion protein, comprising residues 109-122, recapitulates many properties of the full...

The cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replication.

Formation of aberrant protein conformers is a common pathological denominator of different neurodegenerative disorders, such as Alzheimer's disease or prion diseases. Moreover, increasing evidence indicates that soluble oligomers are associated with early pathological alterations and that oligomeric assemblies of different disease-associated proteins may share common structural features. Previo...

Effect of salt on the formation of salt-bridges in β-hairpin peptides.

Salt-bridges ubiquitously form between oppositely charged moieties in proteins. Here we quantify changes in population of salt-bridged β-hairpin peptides due to added salt, and determine the thermodynamic driving forces and cooperativity of salt-bridge formation under these conditions. We find only a fraction of salt-bridged folded conformations at physiologically relevant salt concentrations.

Running Head: De Novo Design of Β-hairpin Antimicrobial Peptides

Structure and Biological Functions of β-Hairpin Antimicrobial Peptides

Antimicrobial peptides (AMPs) are evolutionarily ancient factors of the innate immune system that serve as a crucial first line of defense for humans, animals, and plants against infection. This review focuses on the structural organization, biosynthesis, and biological functions of AMPs that possess a β-hairpin spatial structure. Representatives of this class of AMPs are among the most active ...